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‘My goal? Very modest. Wipe out Rh disease’

Toronto doctor Alvin Zipursky, two decades into retirement, is starting on the biggest challenge of his career.

Dr. Alan Zipursky, known as "Zip" to his colleagues, was among a group of researchers who developed a cure for rhesus disease, a potentially fatal newborn blood disorder, in the 1960s. (Steve Russell / Toronto Star) | Order this photo

Many mornings along University Ave.’s hospital row, an 85-year-old man appears at first glance to be cross-country skiing to work.

If the weather is frigid, as on a recent January day, his head of white hair will be covered by a snug black hat. The orange strap of his leather Roots bag will be crossed over his chest. And while he won’t actually be skiing, of course, he will have a hiking pole grasped in each gloved hand, poking into the sidewalk and helping him keep a brisk pace.

For Dr. Alvin Zipursky, this is part of his regular commute to the Hospital for Sick Children, where he started working in 1981.

Technically, he stopped 20 years ago, when he retired as head of hematology and oncology. But two decades into retirement, whenever he finds himself in Toronto, Zipursky still wakes up every morning in his Bloor St. condo, hurries down University and heads to his crammed, fluorescent-lit cubicle in Sick Kids’ Black Wing.

There is no slowing down for the warm-hearted doctor they call “Zip.” Not because he’s worried about what he’s accomplished — his resumé includes an Order of Canada, 260 published papers, editorship of a major academic journal, developing a university pediatrics department, treating countless kids with blood diseases and cancer, and founding a program for global pediatric research.

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Rather, while his salary has stopped, his insatiable curiosity continues to flow. And what is arguably the biggest challenge of his career is just getting started.

Dr. Alvin Zipursky cuts through U of T's Victoria College as he treks from his Toronto home to his office space at the Hospital for Sick Children. (Steve Russell)

What is Rh, or rhesus hemolytic disease? It is the biggest public health success story that many Canadians under 50 have likely never heard of — probably because they have had no occasion to worry about it.

Rh disease is the penalty for an unlucky toss of the genetic dice, when couples produce a baby whose blood type (Rh positive) is incompatible with the mother’s (Rh negative).

When these and other factors align, the woman’s immune system will betray her: it attacks her baby. “Those whom it kills all die before birth, or shortly thereafter,” author David Zimmerman wrote in Rh: The Intimate History of a Disease and Its Conquest. “Some of the survivors recover; others are left crippled for life in mind and body.”

In the first two-thirds of the last century, Rh disease stalked families across North America. In the United States, it killed up to 10,000 babies every year, according to estimates. For affected women, it was not uncommon to lose two, three or many more babies.

Since the late 1960s, however, a highly effective preventative treatment has virtually eradicated the disease in wealthy nations such as Canada. Today, for Canadian mothers, Rh screening and prevention is just another box to check off on the prenatal to-do list.

But for Zipursky, Rh disease is the medical problem that now bookends his career. As he discovered a few years ago, the disease is far from gone — in the developing world, it is very much a modern-day problem, estimated to kill more than 100,000 newborns a year.

This estimate comes from a paper in Pediatric Research that Zipursky co-authored — the 250th paper he had written.

It may have never happened if not for one of his first papers, a 1959 study he tackled as a research fellow in Winnipeg.

That paper sparked Zipursky’s lifelong interest in Rh. It also became one of the many stepping stones in the global effort to vanquish a deadly disease — a fight that Zipursky once thought was won, and is now determined to finish.

Dr. Alvin Zipursky keeps one of the first vials that held the Rh vaccine, a memento from the early days of research in Winnipeg. (Steve Russell)

Hunt for a cure

When Zipursky was born in Winnipeg on Sept. 27, 1930, the second son of a housewife and an auto shop owner, the term Rh disease had yet to enter the medical lexicon. In fact, doctors had no idea Rh blood types even existed — only 30 years had passed since the world first learned about the ABO blood groups.

This changed in 1940 when scientists discovered the “Rh factor” — a type of protein found on the surface of red blood cells. The vast majority of people have the Rh factor and are considered “Rh positive”; those without it are “Rh negative.” It was named after the rhesus monkey, which also carries the Rh factor and was used in experiments leading to the discovery.

The Rh factor turned out to be the missing piece in a medical puzzle that had long mystified doctors: why some newborns suffer from a devastating disease that can leave them dead or brain-damaged.

Scientists realized that in pregnancies with incompatible blood types, a baby’s Rh factor can trigger the mother’s immune system to produce antibodies that later attack the fetus — a revelation that shattered a “long-cherished myth that the fetus was sealed off” by the womb, according to Zimmerman’s book.

“A mother could kill her unborn or newborn child because their bloods were incompatible!” Zimmerman wrote. “Here was a dramatic disease — which was to call forth some dramatic cures.”

By the early ’50s, the global race to find that cure had taken off — but Zipursky had yet to join. He was still completing medical school, where his passion for pediatrics took root. The University of Manitoba was also where Zipursky met his beloved wife, Freda, with whom he had three sons and shared 52 happy years of marriage (Freda died in 2005).

After stints in Cincinnati and Salt Lake City, Zipursky returned to the University of Manitoba as a research fellow and began his career in pediatric hematology — the study of blood diseases in children.

But the ’50s were lean times for Canadian medical researchers; at one point, Zipursky was juggling five jobs, including one at the Red Cross blood clinic. To fund his research, he also turned to an unexpected source — Playtex Park, a company better known for its girdles, panties and bras.

“Lo and behold, I became a Playtex Park fellow!” Zipursky says with a laugh. “That made my career.”

Using his Playtex funding, Zipursky studied transplacental bleeds: when a baby’s blood cells leak into the mother’s circulation. Employing a new German technique, he discovered that small bleeds occur regularly and published his results in the Lancet — a 1959 paper that was picked up by scientists across the Atlantic.

In Liverpool, a group of researchers were testing a theory for preventing Rh disease: injecting pregnant women with anti-Rh antibodies. But they had encountered a scientific roadblock, which Zipursky’s paper cleared away.

“Crikey!” one of the Liverpool scientists exclaimed when he got his hands on the paper. “Here’s what we’ve been waiting for.”

The group published their first experimental study in 1961, when they successfully injected antibodies into Liverpool policemen, who acted as proxies for pregnant women — an “ingenious method,” according to an accompanying editorial.

Coincidentally, researchers in New York were also pursuing this exact theory and feared “their thunder had been stolen,” according to Zimmerman’s book. New York and Liverpool become the two main theatres in the global battle to develop an Rh prophylaxis.

Back in Winnipeg, however, Zipursky wanted in on the action.

In this gathering of Rh researchers in Hamilton in 1977, Dr. Alvin Zipursky is second from left; fifth from left is Dr. Jack Bowman; and beside him, holding a cane, is Dr. Bruce Chown. The three led Canadian efforts to develop a vaccine. (Steve Russell)

“I said, ‘We should be doing that!’” he says, smacking his hand on the table. “I was going to make Rh immune globulin, the same thing they were using in Liverpool, the same thing they were making in New York. Canada — Winnipeg — became the third group in the world doing prevention of Rh disease.”

Canadian research into the disease was already well underway, led by the renowned Dr. Bruce Chown, who opened Winnipeg’s famous Rh laboratory and devoted his career to understanding the disease.

Zipursky contacted Chown and asked for the names of four women studied by the lab, whose blood had high levels of Rh antibodies. He remembers walking into some of Winnipeg’s poorest neighbourhoods, knocking on the doors of four strangers and asking them a crazy question: will you agree to donate blood once a week?

They all said yes. “They were motivated, because they know what the disease was,” Zipursky said. “They all had dead babies.”

These antibodies became the seed for Canada’s “first preparation of Rh immune globulin,” which was produced by the University of Toronto’s Connaught Laboratories. Chown and his successor at the Rh laboratory, Dr. Jack Bowman, went on to develop the vaccine into a commercial product, called WinRho, which is still in use today.

In 1968, after multiple clinical trials in New York, Liverpool and Canada, an injection to prevent Rh disease was finally licensed — and for families with access to this precious injection, it was the beginning of the end for a deadly newborn disease.

Today, the story of Rh disease is widely regarded as a remarkable achievement in public health — a “strikingly productive series of observations, intuitions, and deductions that have led — within the career span of a single scientific generation — from the elucidation to the defeat of one extremely lethal disease,” according to Zimmerman.

“Rarely is a disease dealt with so effectively in so little time.”

An epiphany from the ‘old guy in a closet’

Just as the race to develop a cure was nearing the finish line, Zipursky left Winnipeg, the Canadian epicentre of the Rh action.

He was hired as chair of the pediatric department at McMaster University, an opportunity he couldn’t pass up. Zipursky continued to work on Rh disease, consulting on the Canadian trials that ultimately led to a vaccine, but his interests also carried him in other directions, including to Sick Kids, where he became head of hematology and oncology.

By the time his mandatory retirement came along in the mid-’90s, Rh disease — as far as Zipursky was concerned — was a problem of the past.

He would eventually realize his folly. But first, something else caught his imagination: global health.

In 1999, Sick Kids was vying to become the editorial seat of a prestigious academic journal, Pediatric Research. Zipursky, who still had an office at the hospital — a “closet-type thing,” as he jokingly calls it — was urged to apply for editor-in-chief.

As Zipursky tells it, the powers that be figured, “Who’s got time? Well, there’s an old guy up there in a closet.”

But according to Margaret Manley-Kucey, a lawyer and longtime collaborator of Zipursky’s, the choice was likely strategic. Not only is Zipursky a respected researcher — a “rock star” of hematology — but he picks up friends and fans everywhere he goes, says Manley-Kucey, now senior manager with Sick Kids’ Centre for Global Child Health.

Within minutes of meeting someone, Zipursky will be calling them “kiddo” and throwing a friendly arm over their shoulder.

“A constant refrain in our office was Zip saying, ‘I’m going to get these five people to this meeting,’ and me saying, ‘You’ll never get them,’” Manley-Kucey recalls. “The next thing you know it’s ‘Yup, they’re coming.’”

At Pediatric Research, Zipursky persuaded the publisher to make studies free online in lower-income countries. Then he got curious: just how many of their papers were relevant to children in the developing world?

“He went into this research bubble … he would forget to eat,” Manley-Kucey recalls. “Then he came back and said, ‘Kiddo, we’ve got a problem. There’s nothing!’

“I sort of shrugged and said, ‘Aw, that’s too bad.’ And he was like, what are we going to do about this?”

Zipursky pushed for the journal to broaden its scope. He opened up a major research meeting to scientists and issues from the developing world. At Sick Kids, he founded the Programme for Global Paediatric Research, which no longer exists but initiated many research efforts that live on.

“He advocated for working on issues in low-income settings,” says Dr. Zulfiqar Bhutta, a respected expert on newborn and child health, who came to Sick Kids from Pakistan after meeting Zipursky. “Over time, not only has that impacted on activities of Sick Kids … (but) other institutions have also been encouraged to develop these kinds of mainstream programs.”

Then, half a century after Zipursky dipped his toe into Rh research, he had an epiphany: “I was sitting in my office thinking, you know, maybe Rh disease isn’t gone.”

Dr. Alvin Zipursky in his office space at the Hospital for Sick Children. Out of that "closet-type thing" that he maintained after his retirement, he began editing the academic journal Pediatric Research and would launch his new push to eradicate Rh disease worldwide. (Steve Russell)

While countries such as Canada have eradicated Rh disease — that is, cases are now rare — immigrant mothers and their babies are still sometimes treated because of lack of care back home. But as far as Zipursky knew, there were no good estimates for those in developing countries.

Rh disease, however, is an easy problem to miss, especially in poor regions. It can only be screened for if mothers know their blood types — challenging in many places. It can be reported only if diagnosed — difficult when many babies die in places where autopsies are rare. And outcomes of Rh disease, such as jaundice, anemia and stillbirths, have many possible causes.

Zipursky investigated the burden of Rh disease in the developing world. In 2013, he and several co-authors published an estimate of the toll there: roughly 100,000 newborn deaths a year, with more than 25,000 babies brain-damaged.

“It’s a real scourge — and it’s solvable,” he says.

Again, Zipursky asked himself: what can I do? With Dr. Vinod Bhutani at Stanford University, he created the Consortium for Universal Rh disease Eradication. He brought others in, including a manufacturer of the Rh vaccine, and tracked down an easy-to-use “lab on a chip” to identify Rh blood types.

Today, pilot projects in India and Ghana are testing whether Rh disease can be effectively screened and prevented in these settings.

“The idea grew because Dr. Zipursky knows so many people,” Bhutani says. “He is the centre, the spoke.”

The impact could be substantial. At one Ghana hospital, about 200 babies a year are affected by Rh disease, according to Dr. Samuel Obed, who works with the consortium.

Nobody thinks globally eradicating Rh will be easy. Its underlying causes are massive: a lack of resources and poor health infrastructure.

But one thing is certain. As long as Rh disease persists, full-time retirement for Zipursky will have to wait.

“He’s had many different retirements from many different roles,” says his son, Bob Zipursky. “It’s always a bit of a family joke. But this is his life and his passion … I don’t think any of us would encourage him to give it up.”

The ‘Rh ladies’ of Winnipeg

In the early 1960s, Dr. Alvin Zipursky recruited four women to donate blood for research on Rh disease. This became the seed for a larger donation program under Dr. Jack Bowman, which ultimately led to a preventative treatment in Canada. The stories behind two of Winnipeg’s “Rh ladies”:

Mary Taillieu poses with three of her four daughters on her 93rd birthday.

Mary Taillieu: ‘The most beautiful veins’

Mary Taillieu has carried eight babies in her womb but only the first, a son, came out healthy.

Her second boy, Gerry, died Nov. 11, 1956 — one day after his birth. Her third son was stillborn; then, a miscarriage. Taillieu gave birth to four daughters, who required massive blood transfusions at birth.

Rh disease stalked her children. After her eighth, she decided: no more dead babies.

And to help other women, she became one of Winnipeg’s “Rh ladies.”

“I decided to join the club,” Taillieu, 93, says from Winnipeg. “I was helping them out, because they helped me out.”

The “club” is really a program started by Zipursky in 1963. He was focused on Rh disease prevention and work was underway to create an injection for pregnant women to protect their babies.

But one ingredient required was the blood of women who had already had the disease. The same antibodies that killed their fetuses were extracted and harnessed as a prophylaxis — when given to other women, it would trick their immune systems and protect their babies.

Zipursky recruited the first four women but had already left by the time Taillieu signed up with Bowman, Zipursky’s successor at the Red Cross blood clinic.

A 1968 Winnipeg Free Press article said the Rh ladies spent two to three hours lying down, as two pints of blood were drawn. The blood was then centrifuged for six minutes, a process called plasmapheresis.

As the blood cells settled at the bottom, the plasma — which contains the antibodies — floated to the top. The blood was then returned to the women, and the plasma shipped to a Toronto lab that processed the prophylaxis.

At the time, 21 women were doing this weekly. The clinic produced enough gamma globulin to supply Canada and other parts of the world, Bowman told the Free Press.

Taillieu gave blood for nearly 15 years, stopping at age 66. She proudly remembers the compliment she used to get at the clinic. “They said I had the most beautiful veins.”

Florentine Bériault and her grown children, Eveline and Emmanuel, in the early '90s.

Florentine Bériault: ‘You’d better start praying …’

An early memory: Eveline Bériault is maybe 5, kneeling with her family inside their Manitoba farmhouse. They are murmuring a bedtime prayer, circled around the kitchen table, when her pregnant mother stands up. Blood drip, drip, drips on the floor.

“She went upstairs and Dad followed her. He said, ‘Prayer’s over. You guys go to bed,’” Bériault recalls. She and her brother retreated to their room and listened as mayhem unfolded.

One neighbour peeked in and told them: “If you don’t want your mother to die tonight, you’d better start praying. I remember kneeling on the bed with the rosary, both of us crying.”

Bériault’s mother would stay in hospital a long time. As Bériault later learned, the baby had succumbed to Rh disease, caused by her parents’ incompatible blood types. Their wedding on June 6, 1944 — D-Day — led to a long and happy marriage but it also produced multiple dead babies.

Eveline and her brother, Emmanuel, are the only Bériault children to survive past birth.

Not that their mother ever complained. Tall and slender, Florentine had the steely resolve of a farmer’s wife. “They were just fighting to put food on the table,” Bériault says. “There was no time for feelings.”

But Florentine was dedicated to giving back to her community, and agreed when approached to donate blood — even though the clinic was an hour away by bus.

Over time, hundreds of needles left painful scar tissue in the crook of her elbows. But Florentine continued donating every week for about a decade. She died in 1994, at 93.

“She talked about helping mothers not have to go through what she went through,” Bériault says. “I was proud of her.”

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